Robert Trivers: The kindness of strangers

The Guardian has posted a very well written and entertaining profile of Robert Trivers, an evolutionary biologist who proposed controversial but influential ideas concerning the emergence of concepts such as altruism and justice as a natural consequence of Darwinian evolution. As with all evolutionary {biology, psychology, computation}, you may readily disagree with the strength of the theories, but it is fun to consider their logical structure. Not to mention Trivers is a guy with an amusing biography and quotes.

Impressive spinal cord regeneration with neural stem cells

Human neural stem cells differentiate and promote locomotor recovery in spinal cord-injured mice — PNAS

This article has some very promising results. I haven’t read the paper in detail, but here’s the executive summary. Human neural stem cells (hNSCs) were injected into mice that received a precision contusion (laminectomy) injury at spinal level T9. Control groups had vehicle and human fibroblast cell injections after receiving the same injury.

The group receiving hNSCs showed a significant functional recovery from the vehicle group. The fibroblast group did not. Then, to prove that the functional recovery was due to the new neurons and glia from the hNSC, the investigators injected the recovered mice with diptheria toxin, which affects human neurons while essentially leaving mouse neurons alone. After the toxin injection, the recovered mice with hNSC regressed back to the same behavioral performance as the vehicle group. That is, the functional recovery reversed after selective de-activation of the hNSC-derived neurons.

Additionally, the hNSCs produced both neurons and oligodendrocytes (myelin producers) in the mice. Through EM, it was verified the hNSC-derived neurons formed synapses with endogenous mouse neurons.

Amazing. Work like this shows how genetically similar mouse and human neurons (well, at least spinal cord neurons) must be. And, with regard to the race to understand and control stem cell development, this provides further evidence of how strongly the local environment can influence differentiation.

Blunt instruments: Schizophrenia drugs

Study Finds Little Advantage in New Schizophrenia Drugs – New York Times

Looks like the current crop of schizophrenia drugs come up short.

The study, which looked at four new-generation drugs, called atypical antipsychotics, and one older drug, found that all five blunted the symptoms of schizophrenia, a disabling disorder that affects three million Americans. But almost three-quarters of the patients who participated stopped taking the drugs they were on because of discomfort or specific side effects.

Damn: Evidence that cursing is hard-wired

Almost Before We Spoke, We Swore – New York Times

Fun article from the NYT about swearing through the ages and its biological basis. Some relevants parts:

Reporting in The Archives of General Psychiatry, Dr. David A. Silbersweig, a director of neuropsychiatry and neuroimaging at the Weill Medical College of Cornell University, and his colleagues described their use of PET scans to measure cerebral blood flow and identify which regions of the brain are galvanized in Tourette’s patients during episodes of tics and coprolalia.

They found strong activation of the basal ganglia, a quartet of neuron clusters deep in the forebrain at roughly the level of the mid-forehead, that are known to help coordinate body movement along with activation of crucial regions of the left rear forebrain that participate in comprehending and generating speech, most notably Broca’s area.

The researchers also saw arousal of neural circuits that interact with the limbic system, the wishbone-shape throne of human emotions, and, significantly, of the “executive” realms of the brain, where decisions to act or desist from acting may be carried out: the neural source, scientists said, of whatever conscience, civility or free will humans can claim.

And some input from Frans about angry chimps:

Indeed, chimpanzees engage in what appears to be a kind of cursing match as a means of venting aggression and avoiding a potentially dangerous physical clash.

Frans de Waal, a professor of primate behavior at Emory University in Atlanta, said that when chimpanzees were angry “they will grunt or spit or make an abrupt, upsweeping gesture that, if a human were to do it, you’d recognize it as aggressive.”

Such behaviors are threat gestures, Professor de Waal said, and they are all a good sign.

Self-replacing network in hippocampus

Some recent work in Neuron (full article; easy to read summary) shows how hippocampal neurons can cause neural progenitor cells to produce new neurons in the hippocampus. I find this fascinating since the network literally is replacing itself through its own dynamics.

The mechanism seems to be that GABAergic cells synapse onto progenitor cells and cause calcium entry due to the depolarization. (GABAergic synapses are often excitatory in young cells which have elevated intracellular chloride levels.) The increased calcium entry leads then to activation of genes coding for neuronal differentiation-related proteins.

Also, here’s some earlier work from Malenka’s lab along the same lines.

Vesicle release in bacteria

Bacterial speech bubbles : Nature

Bacteria secrete signals to other bacteria of the same species through vesicle packets.

Mashburn and Whiteley describe the unexpected convergence of two seemingly unrelated areas of microbiological research: how bacteria talk to their friends, and how they attack their enemies. The authors studied the bacterial pathogen Pseudomonas aeruginosa, which releases a hydrophobic molecule called the ‘pseudomonas quinolone signal’ (PQS) to send messages to other bacteria of the same species. The surprise is that, rather than being secreted as single molecules, PQS is released in bubble-like ‘vesicles’ that also contain antibacterial agents and probably toxins aimed at host tissue cells as well.

I wonder if this is evolutionarily connected to synaptic vesicles or if this is a case of something like convergent evolution…

Big brain genes have been selected for (maybe)

Microcephalin, a Gene Regulating Brain Size, Continues to Evolve Adaptively in Humans — Evans et al. 309 (5741): 1717 — Science

Although the finding itself isn’t terribly shocking, the analysis is interesting and raises some even more interesting ethical questions. Methodology: The researchers tracked the occurence of a particular haplotype, which “increased in frequency too rapidly to be compatible with neutral drift [and] this indicates that it has spread under strong positive selection.” Strikingly this gene is not very old (37,000 years) and it has been changing rapidly… the real message: make no mistake, we’re still evolving!

Another interesting issue involves this figure from the paper:
Map of haplotype distribution for increased brain size

Fig. 3. Global frequencies of Microcephalin haplogroup D chromosomes (defined as having the derived C allele at the G37995C diagnostic SNP) in a panel of 1184 individuals. For each population, the country of origin, number of individuals sampled, and frequency of haplogroup D chromosomes are given (in parentheses) as follows: 1, Southeastern and Southwestern Bantu (South Africa, 8, 31.3%); 2, San (Namibia, 7, 7.1%); 3, Mbuti Pygmy (Democratic Republic of Congo, 15, 3.3%); 4, Masai (Tanzania, 27, 29.6%); 5, Sandawe (Tanzania, 32, 39.1%); 6, Burunge (Tanzania, 28, 30.4%); 7, Turu (Tanzania, 23, 15.2%); 8, Northeastern Bantu (Kenya, 12, 25%); 9, Biaka Pygmy (Central African Republic, 32, 26.6%); 10, Zime (Cameroon, 23, 8.7%); 11, Bakola Pygmy (Cameroon, 24, 10.4%); 12, Bamoun (Cameroon, 28, 17.9%); 13, Yoruba (Nigeria, 25, 24%); 14, Mandenka (Senegal, 24, 16.7%); 15, Mozabite [Algeria (Mzab region), 29, 53.5%]; 16, Druze [Israel (Carmel region), 44, 60.2%]; 17, Palestinian [Israel (Central), 40, 63.8%]; 18, Bedouin [Israel (Negev region), 44, 54.6%]; 19, Hazara (Pakistan, 20, 85%); 20, Balochi (Pakistan, 23, 78.3%); 21, Pathan (Pakistan, 23, 76.1%); 22, Burusho (Pakistan, 25, 66%); 23, Makrani (Pakistan, 24, 62.5%); 24, Brahui (Pakistan, 25, 78%); 25, Kalash (Pakistan, 24, 62.5%); 26, Sindhi (Pakistan, 25, 78%); 27, Hezhen (China, 9, 77.8%); 28, Mongola (China, 10, 100%); 29, Daur (China, 10, 85%); 30, Orogen (China, 10, 100%); 31, Miaozu (China, 9, 77.8%); 32, Yizu (China, 10, 85%); 33, Tujia (China, 10, 75%); 34, Han (China, 41, 82.9%); 35, Xibo (China, 9, 83.3%); 36, Uygur (China, 10, 90%); 37, Dai (China, 9, 55.6%); 38, Lahu (China, 10, 85%); 39, She (China, 9, 88.9%); 40, Naxi (China, 10, 95%); 41, Tu (China, 10, 75%); 42, Cambodian (Cambodia, 11, 72.7%); 43, Japanese (Japan, 27, 77.8%); 44, Yakut [Russia (Siberia region), 25, 98%]; 45, Papuan (New Guinea, 17, 91.2%); 46, NAN Melanesian (Bougainville, 18, 72.2%); 47, French Basque (France, 24, 83.3%); 48, French (France, 28, 78.6%); 49, Sardinian (Italy, 26, 90.4%); 50, North Italian [Italy (Bergamo region), 13, 76.9%]; 51, Tuscan (Italy, 8, 87.5%); 52, Orcadian (Orkney Islands, 16, 81.3%); 53, Russian (Russia, 24, 79.2%); 54, Adygei [Russia (Caucasus region), 15, 63.3%]; 55, Karitiana (Brazil, 21, 100%); 56, Surui (Brazil, 20, 100%); 57, Colombian (Colombia, 11, 100%); 58, Pima (Mexico, 25, 92%); 59, Maya (Mexico, 25, 92%).

Haplogroup D describes a set of mutations in the gene encephalin that, according to the study, have been selected for. The figure/caption above shows that this haplotype occurs at a much lower rate in sub-Saharan populations and highest in East Asian, European, and Latin American populations. Let me be clear: The paper is intended to demonstrate the selective pressure for this haplogroup. Although the authors suggest it, this does not necessarily give us the causal connection that encephalin was selected for because the gene results in a bigger brain.

It is known that encephalin definitely plays a role in determing brain size, but, as this well done NYT article (highly recommended for those unable to access the original Science article) points out, there could be another function of the gene product (perhaps even some non-neural role) that explains the selection.

I do feel strongly that this kind of science is interesting and needs to be done, both for improving our understanding of the world and for public health benefits, but it will be only more controversial as we find more genes and evolutionary scenarios like this. One very nice side-effect I think is that these new levels of individual genotyping precision will really challenge what we think of as race. Once we discover everyone is a genetic mutt, can anyone really be said to belong to one race? .

Jimbo et al '99: plasticity at the network level in culture

Jimbo, Tateno, and Robinson did a network plasticity experiment using cultured networks and a multi-electrode array.

They determine the effect of a tetanus at one electrode in a network on the network. Specifically, they look at how the tetanus potentiates or depresses the ability of a test pulse at another electrode to evoke spike trains at various neurons across the network.

They grew cultures on a MEA for a month. They stimulated each electrode in succession with a test pulse. They recorded the response at all electrodes after each test pulse. They used spike sorting to identify the reponses of individual neurons out of the electrode traces. They found that the network’s response to a given test pulse was reproducable for about 50ms after the test pulse.

Then they applied a strong stimulus (a tetanus) to a single electrode (to make it learn 🙂 ). After that they re-characterized the network’s responses to test pulses at every site.

They found that some electrode sites became more potent (“potentiated response”) after the tetanus was applied. This means that, when a test pulse was applied to this electrode site, neurons in all areas of the network responded either the same, or more strongly than they had before the tetanus.

Other sites became less potent (“depressed response”) after the tetanus was applied.

Surprisingly, it was very rare for any given electrode site to become better at stimulating some neurons and worse at stimulating others as a result of the tetanus.

What determined which electrode sites became potentiated and which ones became depressed? The tetanus potentiated electrodes which evoked spike trains that tended to contain spikes which were within 40ms of the spike trains evoked by the tetanus electrode, and depressed others. That is, it potentiated sites which evoked patterns similar to the patterns evoked by the tetanus site.

However, the spike trains evoked by both potentiated and depressed neurons became more synchronized with the tetanus electrode after applying the tetanus.

See page 5 of “Distributed processing in cultured neuronal networks” for another review of this work.

See this NeuroWiki page for more details (the strange {{}} over there are because we will soon have footnotes).

Jimbo, Y., Tateno, T., and Robinson, H. P. C.,
Simultaneous Induction of Pathway-Specific Potentiation and Depression in Networks of Cortical Neurons. Biophysical Journal, 1999. 76: p. 670-678.

Amplification using recurrent connectivity

This post has much the same content as this NeuroWiki page; you may wish to read and comment on it there.

I’ve only skimmed this interesting article, so beware that I may not correctly understand it.

This article proposes that recurrent excitation in cortex leads to amplification, and analyzes this using the mathematics of basic amplifiers (taught in introductory electrical engineering courses; i.e. open-loop gain and closed loop gain).

They construct a simulation based on this principal that agrees with some electrophysiological and pharmacological results from neurobiology experiments in layer IV of V1.

At the end, they conjecture that a sensory network could use this principal for noise reduction and possibly pattern recognition.

Douglas, Rodney J.; Koch, Christof; Mahowald, Misha; Martin, Kevan A. C.; Suarez, Humbert H. Recurrent Excitation in Neocortical Circuits. Science, Volume 269, Issue 5226, pp. 981-985.

Real-time feedback in MEAs: review paper

This is a review paper by Steve Potter, Daniel Wagenaar, and Thomas DeMarse on real-time closed-loop feedback control applied to neuronal cultures using MEAs. That is, you stimulate the cultures with a pattern that depends upon what you’re reading from them. This paper seems to be targeted at people who want to start doing these sorts of experiments; most of it is a very readable overview on how to setup a rig to do this, with pointers to other papers that cover the specifics. However, there are a couple of pages summarizing recent research using these techniques.

I’d recommend reading this paper if you want to setup a rig to do this; otherwise, I’d recommend reading pages 18 and 19.

S. M. Potter, D. A. Wagenaar, T. B. DeMarse. Closing the loop: Stimulation feedback systems for embodied MEA cultures. In: Advances in network electrophysiology using multi-electrode arrays, M. Taketani, M. Baudry, eds. Kluwer, New York. In press.